title: Sterol regulatory element-binding protein-1/fatty acid synthase involvement in proliferation inhibition and apoptosis promotion induced by progesterone in endometrial cancer.
abstract: BACKGROUND
  The number of endometrial cancer (EC) cases is escalating rapidly, with no evident improvements in survival rates. The downregulation of progesterone receptor, resulting in progestin resistance, is presently a major problem regarding the therapeutic aspect. On the basis of this, we can focus more on the downstream signaling pathways that are controlled by progesterone. Lipid biosynthesis mediated by sterol regulatory element-binding protein-1/fatty acid synthase (SREBP-1/FASN) is of utmost importance to the growth and the proliferation of EC cells, so we hypothesize that SREBP-1/FASN might be involved in suppressing the proliferation and promoting apoptosis in EC cells through the effects induced by progesterone.
  
  
  METHODS
  The Cell Counting Kit-8 was used to analyze the growth inhibition ratio of Ishikawa cells upon treatment with megestrol acetate (MA; MA is a progesterone derivative, also known as 17α-acetoxy-6-dehydro-6-methylprogesterone) and to determine the 50% inhibitory concentration. Apoptosis ratio was analyzed by treatment of the cells with MA at 50% inhibitory concentration at different time intervals using Annexin V-FITC/propidium iodide. The protein and messenger RNA levels of SREBP-1 and FASN were compared between the experimental and control groups (MA-treated Ishikawa cells were considered to be the experimental group).
  
  
  RESULTS
  The experimental group showed obvious growth inhibition that was time and concentration dependent. The apoptosis ratio was also significantly higher in the experimental group compared with the control group (P < 0.01). The protein and messenger RNA levels of SREBP-1 and FASN were significantly reduced by MA too.
  
  
  CONCLUSIONS
  Sterol regulatory element-binding protein-1/FASN is involved in the proliferation suppression and apoptosis promotion brought about by MA in Ishikawa cells.
authors.affiliation: *Department of Obstetrics and Gynecology, Qi Lu Hospital, Shangong University, Jinan, Shandong, China; †Department of Pharmaceutical Chemistry, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China; and ‡Physical Examination Centre, Qi Lu Hospital, Shangong University, Jinan, Shandong, China.
authors.forename: Chunping
authors.initials: C
authors.lastname: Qiu
authors.forename: Samina
authors.initials: S
authors.lastname: Dongol
authors.forename: Qing-Tao
authors.initials: QT
authors.lastname: Lv
authors.forename: Ximei
authors.initials: X
authors.lastname: Gao
authors.forename: Jie
authors.initials: J
authors.lastname: Jiang
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D016889:Endometrial Neoplasms / Q000235:genetics / Q000473:pathology*; D054890:Fatty Acid Synthase, Type I / Q000502:physiology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D019290:Megestrol Acetate / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000502:physiology*
chemical_list: D018931:Antineoplastic Agents, Hormonal; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D011374:Progesterone; C518729:FASN protein, human; D054890:Fatty Acid Synthase, Type I; D019290:Megestrol Acetate